Impact of gestational diabetes mellitus treatment on medium/long-term outcomes after pregnancy: A systematic review and meta-analysis.

AIM: We aimed to evaluate the effect of gestational diabetes mellitus (GDM) treatment on medium/long-term outcomes both the mother and offspring. METHODS: We performed a systematic review on randomized clinical trials addressing specific treatment of women with GDM versus usual care and its impact on maternal and offspring outcomes at medium/long-term. MEDLINE, EMBASE and CENTRAL were searched from inception to 8 October 2021. OUTCOME VARIABLES: maternal (diabetes, metabolic syndrome, 12 secondary); offspring (diabetes, impaired fasting glucose, impaired glucose tolerance, high body mass index, 15 secondary). Risk of bias was assessed with Cochrane tool and aggregation performed with Revman 5.4. RESULTS: We included five studies (1140 women, 767 offspring) with follow-up ranging 4-16 years after delivery. GDM treatment likely does not reduce risk of maternal diabetes (RR 1.00; [95% CI 0.82-1.23]) and may not reduce that of metabolic syndrome (RR 0.93; [95% CI 0.71-1.22]). We obtained very uncertain evidence that treatment may increase maternal HDL-cholesterol. Findings showed that GDM treatment may not have an impact on infants' outcomes (RRs 0.79; [95% CI 0.39-1.69] for impaired fasting glucose; RR 0.91; [95% CI 0.74-1.12] for body mass index >85th centile and 0.89; [95% CI 0.65-1.22] for body mass index >95th centile respectively). CONCLUSIONS: With current evidence is uncertain if specific treatment of women with GDM has an impact on medium/long-term metabolic outcomes either in the mother or in the offspring. These results add evidence to the recommendation of systematically reevaluating mother and offspring after delivery. REGISTRATION: OSF, DOI 10.17605/OSF.IO/KFN79.

Gestational Diabetes Mellitus and Diet: A Systematic Review and Meta-analysis of Randomized Controlled Trials Examining the Impact of Modified Dietary Interventions on Maternal Glucose Control and Neonatal Birth Weight.

OBJECTIVE: Medical nutrition therapy is a mainstay of gestational diabetes mellitus (GDM) treatment. However, data are limited regarding the optimal diet for achieving euglycemia and improved perinatal outcomes. This study aims to investigate whether modified dietary interventions are associated with improved glycemia and/or improved birth weight outcomes in women with GDM when compared with control dietary interventions. RESEARCH DESIGN AND METHODS: Data from published randomized controlled trials that reported on dietary components, maternal glycemia, and birth weight were gathered from 12 databases. Data were extracted in duplicate using prespecified forms. RESULTS: From 2,269 records screened, 18 randomized controlled trials involving 1,151 women were included. Pooled analysis demonstrated that for modified dietary interventions when compared with control subjects, there was a larger decrease in fasting and postprandial glucose (-4.07 mg/dL [95% CI -7.58, -0.57]; P = 0.02 and -7.78 mg/dL [95% CI -12.27, -3.29]; P = 0.0007, respectively) and a lower need for medication treatment (relative risk 0.65 [95% CI 0.47, 0.88]; P = 0.006). For neonatal outcomes, analysis of 16 randomized controlled trials including 841 participants showed that modified dietary interventions were associated with lower infant birth weight (-170.62 g [95% CI -333.64, -7.60]; P = 0.04) and less macrosomia (relative risk 0.49 [95% CI 0.27, 0.88]; P = 0.02). The quality of evidence for these outcomes was low to very low. Baseline differences between groups in postprandial glucose may have influenced glucose-related outcomes. As well, relatively small numbers of study participants limit between-diet comparison. CONCLUSIONS: Modified dietary interventions favorably influenced outcomes related to maternal glycemia and birth weight. This indicates that there is room for improvement in usual dietary advice for women with GDM.

Pharmacotherapy for hyperglycemia in pregnancy - Do oral agents have a place?

Diabetes is a frequent condition in pregnancy and achieving adequate glycemic control is of paramount importance. Insulin treatment is the gold standard, oral agents are more attractive, but their safety and efficiency should be a prerequisite for their use. We have more information regarding treatment of women with gestational diabetes mellitus where glyburide can induce a picture of fetal hyperinsulinism (higher birthweight and more neonatal hypoglycemia) whereas metformin requires supplemental insulin in a larger proportion of women but achieves satisfactory perinatal outcomes with the exception of preterm birth. Information in patients with Type 2 Diabetes Mellitus is much more limited but also favors metformin. Combinations provide additional possibilities. However, as to long-term outcomes, we have no information on the impact of exposure to glyburide and it is still unclear if in utero exposure to metformin will have any effect on the offspring and the direction of this effect. Women prefer oral agents, indicating the need of additional studies.

Systematic review and meta-analysis on the association of prepregnancy underweight and miscarriage.

BACKGROUND: Maternal underweight, overweight and obesity have been associated with a higher risk of miscarriage. Most individual reports and all meta-analyses have addressed high body mass index. OBJECTIVES: To review the literature and summarize the risk of miscarriage in underweight women vs those with normal weight. METHODS: A Medline Search (1st January 1990-20th November 2015, human, in English, French, Italian, Spanish or Portuguese) was conducted. Both spontaneous pregnancies and pregnancies after assisted reproduction techniques were considered. Cohort and case control studies were included if they reported data on the outcome of interest (clinical miscarriage), in underweight and normal weight women. Information on clinical miscarriage in other body mass index categories was collected when available. Two investigators reviewed the abstracts, full text papers and extracted data. Review Manager 5.1 software was used to summarize the results. RESULTS: 32 studies (30 cohort, 2 case control) and a total of 265,760 women were included. In cohort studies, the relative risk (RR) of clinical miscarriage in underweight women was 1.08, 95% CI 1.05-1.11; p<0.0001). The corresponding figures were RR 1.09, 95% CI 1.04-1.13; p<0.0001 for overweight women and RR 1.21, 95% CI 1.15-1.27; p<0.00001 for obese women. In case control studies, the odds ratio (OR) of clinical miscarriage in underweight women was 1.02, 95% CI 0.46-2.30; p=0.95). The corresponding figures were OR 1.01, 95% CI 0.88-1.16; p=0.89 for overweight women and OR 1.26, 95% CI 1.01-1.57; p=0.04 for obese women. The limitations of this study are that it is restricted to studies with information on underweight women and that I2 ranges from 0 to 91% in different subgroups. CONCLUSION: We conclude that maternal underweight is associated with a slightly increased risk of clinical miscarriage, similar to that of overweight women and lower than the risk observed in obesity. The heterogeneity displayed in some subgroups limits the strength of the conclusion.

Glibenclamide, metformin, and insulin for the treatment of gestational diabetes: a systematic review and meta-analysis.

OBJECTIVE: To summarize short term outcomes in randomized controlled trials comparing glibenclamide or metformin versus insulin or versus each other in women with gestational diabetes requiring drug treatment. DESIGN: Systematic review and meta-analysis. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomized controlled trials that fulfilled all the following: (1) published as full text; (2) addressed women with gestational diabetes requiring drug treatment; (3) compared glibenclamide v insulin, metformin v insulin, or metformin v glibenclamide; and (4) provided information on maternal or fetal outcomes. DATA SOURCES: Medline, CENTRAL, and Embase were searched up to 20 May 2014. OUTCOMES MEASURES: We considered 14 primary outcomes (6 maternal, 8 fetal) and 16 secondary (5 maternal, 11 fetal) outcomes. RESULTS: We analyzed 15 articles, including 2509 subjects. Significant differences for primary outcomes in glibenclamide v insulin were obtained in birth weight (mean difference 109 g (95% confidence interval 35.9 to 181)), macrosomia (risk ratio 2.62 (1.35 to 5.08)), and neonatal hypoglycaemia (risk ratio 2.04 (1.30 to 3.20)). In metformin v insulin, significance was reached for maternal weight gain (mean difference -1.14 kg (-2.22 to -0.06)), gestational age at delivery (mean difference -0.16 weeks (-0.30 to -0.02)), and preterm birth (risk ratio 1.50 (1.04 to 2.16)), with a trend for neonatal hypoglycaemia (risk ratio 0.78 (0.60 to 1.01)). In metformin v glibenclamide, significance was reached for maternal weight gain (mean difference -2.06 kg (-3.98 to -0.14)), birth weight (mean difference -209 g (-314 to -104)), macrosomia (risk ratio 0.33 (0.13 to 0.81)), and large for gestational age newborn (risk ratio 0.44 (0.21 to 0.92)). Four secondary outcomes were better for metformin in metformin v insulin, and one was worse for metformin in metformin v glibenclamide. Treatment failure was higher with metformin than with glibenclamide. CONCLUSIONS: At short term, in women with gestational diabetes requiring drug treatment, glibenclamide is clearly inferior to both insulin and metformin, while metformin (plus insulin when required) performs slightly better than insulin. According to these results, glibenclamide should not be used for the treatment of women with gestational diabetes if insulin or metformin is available.Systematic review registration NCT01998113.

Ultrasound-guided compared to conventional treatment in gestational diabetes leads to improved birthweight but more insulin treatment: systematic review and meta-analysis.

OBJECTIVE: To perform a systematic review and meta-analysis of randomized controlled trials assessing ultrasound-guided versus conventional management in women with a broad severity-spectrum of gestational diabetes mellitus. DESIGN: Systematic review and meta-analysis of trials published until August 2012. SETTING: PubMed and Web of Science databases. STUDY SELECTION AND METHODS: Eighteen studies were reviewed in full text. Eligibility criteria were (i) randomized controlled trials comparing metabolic management in women with gestational diabetes mellitus and ultrasound-based vs. the conventional management to assess fetal growth, (ii) representative of the whole spectrum of hyperglycemia and fetal growth, (iii) data on perinatal outcomes. Review Manager 5.0 was used to summarize the results. RESULTS: Two studies fulfilled inclusion criteria. The ultrasound-guided group had a lower rate of large-for-gestational age newborns (relative risk 0.58, 95% confidence interval 0.34-0.99), macrosomia (relative risk 0.32, 95% confidence interval 0.11-0.95) and abnormal birthweight (small/large-for-gestational age, relative risk 0.64, 95% confidence interval 0.45-0.93) and a higher rate of insulin treatment (relative risk 1.58, 95% confidence interval 1.14-2.20). The number of women with gestational diabetes with a need to treat to prevent an additional newborn with abnormal birthweight was 10. CONCLUSIONS: In women with a broad severity-spectrum of gestational diabetes mellitus, ultrasound-guided management improves birthweight distribution, but increases the need for insulin treatment. More research is needed in this area because results are derived from a limited number of patients.

Major congenital malformations in women with gestational diabetes mellitus: a systematic review and meta-analysis.

BACKGROUND: The risk of major congenital malformations (MCM) is increased in women with pregestational diabetes mellitus (PGDM). Whether this risk is increased in gestational diabetes mellitus (GDM) is still debated. The aim of this study was to perform a systematic review (and meta-analysis) of major congenital malformations in women with gestational diabetes versus a reference population. METHODS: We conducted a MEDLINE search (1 January 1995 to 31 December 2009) of original studies reporting data on major congenital malformations in women with gestational diabetes and a reference group. Information on pregestational diabetes was collected when available. Two investigators considered studies for inclusion and extracted data; discrepancies were solved by consensus. Meta-analysis tools were used to summarize results. MOOSE and PRISMA guidelines were followed. RESULTS: Two case control and 15 cohort studies were selected out of 3488 retrieved abstracts. A higher risk of major congenital malformations was observed in offspring of women with gestational diabetes with the following relative risk (RR)/odds ratios (OR) and 95% confidence intervals (CI): RR 1.16 (1.07-1.25) in cohort studies and OR 1.4 (1.22-1.62) in case control studies. Risk of major congenital malformations was much higher in offspring of women with PGDM than in those of the reference group: RR 2.66 (2.04-3.47) in cohort studies and OR 4.7 (3.01-6.95) in the single case control study providing information. CONCLUSION: There is a slightly higher risk of major congenital malformations in women with gestational diabetes than in the reference group. The contribution of women with overt hyperglycemia and other factors could not be ascertained. This risk, however, is much lower than in women with pregestational diabetes.

Prognostic factors and follow-up of patients with differentiated thyroid carcinoma with false negative or nondiagnostic FNAC before surgery. Comparison with a control group.

Since the clinical implementation of fine needle aspiration cytology (FNAC) to diagnose thyroid carcinoma, few patients remain misdiagnosed and little is known about their clinical outcomes. An observational retrospective study was carried out to analyse prognostic factors and follow-up of patients with differentiated thyroid carcinoma (DTC) not disclosed by FNAC before surgery, compared to a control group. From October 2003 to July 2010, 308 patients underwent surgery as treatment for nodular goitre and 53 had DTC. Cases were 12 subjects with DTC and benign (n = 7) or nondiagnostic (n = 5) FNAC. Controls were 39 subjects with DTC and suspicious (n = 19) or malignant (n = 20) FNAC. Prognostic factors, recurrence and survival rates were compared. Cases had longer time from FNAC to surgery than the control group (86.8 ± 74.1 vs. 16.4 ± 23.8 weeks; P < 0.001), higher prevalence of follicular carcinoma (33.3 vs. 2.6%; P = 0.009), and of two-time total thyroidectomy (75 vs. 30.8%; P = 0.016). Average follow-up was 42.7 ± 25.3 months (2-86 months). There were no deaths. Disease-free survival for cases was 66.9 ± 5.8 months, and for controls 78.7 ± 3.9 months (P: ns). In patients with DTC, the result of the FNAC performed before surgery was not an independent predictor of recurrences or mortality in the first 7 years of follow-up. Thus, false negative or nondiagnostic FNAC in a patient with DTC does not seem to be a primary prognostic factor, but it may reveal other adverse prognostic factors such as longer time to therapy and higher prevalence of follicular carcinoma that may influence long-term outcomes.

Complex thyroid nodules with nondiagnostic fine needle aspiration cytology: histopathologic outcomes and comparison of the cytologic variants (cystic vs. acellular).

Management of complex thyroid nodules (CTN) is a common dilemma due to their high prevalence and frequent nondiagnostic fine needle aspiration cytology (FNAC). In order to know the rate of malignancy, we reviewed our experience about histopathologic diagnosis of CTN with nondiagnostic FNAC, and we analyzed if cytological variants of nondiagnostic FNAC indicated different histopathologic outcomes. We conducted a review of 927 consecutive aspirations performed between 2003 and 2008. We selected patients without history of radiation, with echographic CTN, and nondiagnostic FNAC, who underwent surgery. We analyzed histopathologic results and compared patients with benign and malignant nodules, and searched for differences between patients with cystic changes in FNAC (C-FNAC), and patients with acellular or only bloody FNAC (A-FNAC). Thirty-six patients were included (mean age 45.7 ± 13 years; 30 females). Four patients had malignant nodules; all were papillary carcinomas. Patients with benign nodules had a similar profile to patients with malignant nodules. Patients with C-FNAC (n = 21) were younger (41.3 ± 12.6 vs. 51.8 ± 11.2 years; P < 0.02), had more lymphocytic thyroiditis (33.3 vs. 0%; P < 0.02), a slightly higher rate of carcinoma in the nodule (14.3 vs. 6.6%; P: ns), and also of papillary microcarcinoma outside the nodule (9.6 vs. 0%; P: ns) than patients with A-FNAC. In conclusion, we report an 11.1% malignancy rate in CTN with nondiagnostic FNAC. Nodules with C-FNAC variant had a slightly higher rate of malignancy than A-FNAC, which may be in relation with younger age and higher prevalence of lymphocytic thyroiditis in this group of patients.

Parathyroid carcinoma in multiple endocrine neoplasia type 1. Case report and review of the literature.

Parathyroid carcinoma is an infrequent cause of primary hyperparathyroidism. Although hyperparathyroidism in multiple endocrine neoplasia 1 (MEN1) syndrome is the most common manifestation, parathyroid carcinoma is rare. We report a male patient who was diagnosed at 44 years of age with parathyroid carcinoma in the context of MEN1 syndrome coincident with a malignant gastrinoma and non-functioning adrenal adenomas. A genetic analysis revealed the mutation W183C in exon 3 of the MEN1 gene. The diagnosis of carcinoma was made after parathyroid surgery; there had been no clinical suspicion prior to surgery, as the patient had presented only moderate hypercalcemia. Our review of the few published cases of parathyroid carcinoma in MEN1 syndrome reported in the literature indicates that MEN1 gene mutations do not confer a greater risk for parathyroid carcinoma and do not appear to differ from sporadic parathyroid carcinoma.

Maternal and fetal outcome in women with type 2 versus type 1 diabetes mellitus: a systematic review and metaanalysis.

CONTEXT: Glycemic disturbance is usually less severe in pregnant women with type 2 than in those with type 1 diabetes mellitus (DM). Nevertheless, a worse perinatal outcome in women with type 2 DM has been reported in some studies. OBJECTIVE: Our objective was to review maternal and fetal outcomes in pregnant women with type 2 vs. type 1 DM. STUDY SELECTION: We conducted a systematic review of papers providing original data on pregnancy outcomes in both type 2 and type 1 DM (Medline search of the period January 1, 1987, to June 30, 2008). Two independent investigators considered papers for eligibility, and a third one solved discrepancies. DATA EXTRACTION: Metaanalysis tools were used to compare four main outcomes (major congenital malformations, stillbirth, and neonatal and perinatal mortality) and 15 secondary ones (five maternal, 10 fetal). Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were used to assess quality. DATA SYNTHESIS: Thirty-three studies qualified for inclusion of 3743 citations retrieved. Women with type 2 DM had lower glycated hemoglobin (HbA1c) at booking and throughout pregnancy but a higher risk of perinatal mortality [odds ratio (OR) 1.50, 95% confidence interval (CI) 1.15-1.96] without significant differences in the rates of major congenital malformations, stillbirth, and neonatal mortality. As to secondary outcomes, women with type 2 DM had less diabetic ketoacidosis (OR 0.09, 95% CI 0.02-0.34) and cesarean section (OR 0.80, 95% CI 0.59-0.94) without differences in other outcomes. CONCLUSIONS: Despite a milder glycemic disturbance, women with type 2 DM had no better perinatal outcomes than those with type 1, indicating that type 2 DM in pregnancy is a serious condition.